Chemoradiotherapy with TS-1/camptothecins

Abstract

An antitumor agent for chemoradiotherapy of rectal cancer comprising a combination of TS-1 (a combination drug of tegafur, gimeracil, and oteracil potassium at a 1:0.4:1 molar ratio) and CPT-11 (irinotecan hydrochloride). The antitumor agent of the invention can achieve marked tumor volume reduction without causing major side effects, especially by coadministering it with preoperative radiation therapy. The volume of even large tumors that are refractory to surgical resection can be reduced by coadministering the antitumor agent of the invention with preoperative radiation therapy, making the subsequent surgical resection of the tumor easier.

1 . Chemoradiotherapy for rectal cancer, comprising radiation irradiation in combination with administration of tegafur in a therapeutically effective amount, gimeracil in an amount effective for potentiating the antitumor effect, oteracil potassium in an amount effective for inhibiting side effects, and camptothecin or a camptothecin derivative in a therapeutically effective amount.  
     
     
         2 . The chemoradiotherapy according to  claim 1 , wherein the camptothecin derivative is irinotecan hydrochloride.  
     
     
         3 . The chemoradiotherapy according to  claim 1 , wherein the molar ratio of tegafur, gimeracil, and oteracil potassium is 1:0.1˜5:0.1˜5.  
     
     
         4 . The chemoradiotherapy according to  claim 3 , wherein the molar ratio of tegafur, gimeracil, and oteracil potassium is 1:0.4:1.  
     
     
         5 . The chemoradiotherapy according to  claim 4 , wherein a combination drug of tegafur, gimeracil and oteracil potassium with a molar ratio of 1:0.4:1 is administered in an amount of about 10 to about 200 mg/m 2 /day, based on the tegafur; irinotecan hydrochloride is administered in an amount of about 10 to about 200 mg/ 2 /day; and the radiation dose is in a range of 40 to 60 Gy per course.  
     
     
         6 . The chemoradiotherapy according to  claim 5 , wherein the combination drug containing tegafur, gimeracil and oteracil potassium at a molar ratio of 1:0.4:1 is administered in an amount of about 80 mg/m 2 /day, based on the tegafur, on Days 1 to 5, 8 to 12, 22 to 26, 29 to 33; the irinotecan hydrochloride is administered in an amount of about 80 mg/m 2 /day on Days 1, 8, 22 and 29; and 1.8 Gy/day of radiation is administered on Days 1 to 5, 8 to 12, 15 to 19, 22 to 26 and 29 to 33.  
     
     
         7 . The chemoradiotherapy according to  claim 1 , wherein the disease stage of the patient to undergo treatment is T3 or T4 in terms of depth of wall invasion and falls within a range of N0 to N3 in terms of lymph node metastasis according to the rectal cancer staging system.  
     
     
         8 . The chemoradiotherapy according to  claim 7 , which is performed prior to surgical resection of the tumor.  
     
     
         9 . An antitumor agent for use in chemoradiotherapy of rectal cancer, comprising a combination of tegafur in a therapeutically effective amount, gimeracil in an amount effective for potentiating an antitumor effect, oteracil potassium in an amount effective for inhibiting side effects, and camptothecin or a camptothecin derivative in a therapeutically effective amount.  
     
     
         10 . The antitumor agent according to  claim 9 , wherein the camptothecin derivative is irinotecan hydrochloride.  
     
     
         11 . The antitumor agent according to  claim 9 , wherein the molar ratio of tegafur, gimeracil and oteracil potassium is 1:0.1˜5:0.1˜5.  
     
     
         12 . The antitumor agent according to  claim 11 , wherein the molar ratio of tegafur, gimeracil and oteracil potassium is 1:0.4:1.  
     
     
         13 . The antitumor agent according to  claim 9 , which is used for preoperative chemoradiotherapy of rectal cancer.  
     
     
         14 . An antitumor agent for use in chemoradiotherapy of rectal cancer, which is a pharmaceutical formulation consisting of two or more preparations containing tegafur, gimeracil, oteracil potassium, and camptothecin or a camptothecin derivative, which preparation each comprises one or any combination of said active ingredients, or which is a pharmaceutical formulation consisting of a single preparation containing all of the active ingredients.  
     
     
         15 . The antitumor agent according to  claim 14 , wherein the camptothecin derivative is irinotecan hydrochloride.  
     
     
         16 . The antitumor agent according to  claim 14 , wherein the molar ratio of tegafur gimeracil and oteracil potassium is 1:0.1˜5:0.1˜5.  
     
     
         17 . The antitumor agent according to  claim 16 , wherein the molar ratio of tegafur, gimeracil and oteracil potassium is 1:0.4:1.  
     
     
         18 . The antitumor agent according to  claim 14 , which comprises a combination drug containing tegafur, gimeracil and oteracil potassium as the active ingredients and a preparation containing irinotecan hydrochloride as the active ingredient.  
     
     
         19 . The antitumor agent according to  claim 14 , which is used for preoperative chemoradiotherapy for rectal cancer.  
     
     
         20 . A kit for use in chemoradiotherapy of rectal cancer, which comprises a combination of (a) a combination drug containing tegafur in a therapeutically effective amount, gimeracil in an amount effective for potentiating an antitumor effect, oteracil potassium in an amount effective for inhibiting side effects, and (b) a preparation of camptothecin or a camptothecin derivative in a therapeutically effective amount.  
     
     
         21 . The kit according to  claim 20 , wherein the camptothecin derivative is irinotecan hydrochloride.  
     
     
         22 . The kit according to  claim 20 , wherein the molar ratio of tegafur, gimeracil, and oteracil, potassium is 1:0.1˜5:0.1˜5.  
     
     
         23 . The kit according to  claim 22 , wherein the molar ratio of tegafur, gimeracil and oteracil potassium is 1:0.4:1.  
     
     
         24 . The kit according to  claim 20 , which is used for preoperative chemoradiotherapy for rectal cancer.